The overall objective of this research proposal is to elucidate the factors, particularly hormonal, which regulate riboflavin metabolism. The specified aims of the proposal are as follows: (a) Explore further the relation of thyroid hormone and riboflavin in tadpole metamorphosis. (b) Study the conversion of C14 riboflavin to C14-FMN and C14-FAD in liver of normal and riboflavin-deficinet, hyperthroid and hypothyroid animals. (c) Explore the binding of FAD to the apoenzyme of glutathiose reductase and its possible relation to altered thyroid function; measure erythrocyte glutathione reductase activity in patients with hyperthyroidism and myxedema. (d) Determine by tissue fractionation, the nature of stimulation of riboflavin metabolism in brain. (e) Apply the principle of competitive protein binding assay of riboflavin to biological fluids other than urine, and to pharmacentical preparations. Utilize the method for metabolic studies and for nutritional surveys. (f) Determine the pathogenesis of disturbed taste and smell sensations in patients with primary hypothyroidism, the time course of their development and response to treatment, and the role of this sympton complex in the clinical status of the patients as a whole. (g) Widen the spectrum of endocrine studies of riboflavin metabolism in animals and in man, particularly in relation to estrogen, insulin, ACTH and the adrenal corticoids. (h) Evaluate thyroid function in riboflavin-deficient animals by measuring hormone turnover, and by assaying activities of enzymes which degrade thyroid hormone.